Pharmacological interventions for ADHD: a systematic review and dose-effect network meta-analysis
Mikail Nourredine1, Lucie Jurek2, Tasnim Hamza3
1Developmental "Evidence synthesis, Prediction, Implementation" (EPI) Lab, Centre for Innovation in Mental Health, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Department of Biostatistics, Hospices civils de Lyon, Lyon, France; CNRS, LBBE, UMR 5558, Université Claude Bernard Lyon 1, Lyon, France.
The Lancet. Psychiatry
|May 14, 2026
Summary
Optimizing attention-deficit/hyperactivity disorder (ADHD) medication dosage is crucial. This study reveals distinct dose-effect patterns for ADHD drugs in children and adults, guiding better treatment decisions and avoiding suboptimal prescribing or excessive escalation.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Optimizing medication dosage for ADHD is essential for maximizing treatment benefits.
- Current clinical guidelines offer limited information on ADHD medication dosing.
- Concerns exist regarding subtherapeutic prescribing for ADHD.
Purpose of the Study:
- To estimate dose-effect curves for the efficacy and tolerability of ADHD medications.
- To analyze these dose-effect relationships across different age groups.
- To provide evidence for optimizing ADHD pharmacological treatment.
Main Methods:
- Systematic review and dose-effect network meta-analysis of double-blind randomized controlled trials (RCTs).
- Included oral monotherapy for ADHD in individuals aged 5 years and older.
- Analyzed efficacy and tolerability (discontinuation due to adverse events) using hierarchical Bayesian models.
Main Results:
- Distinct dose-effect patterns were observed for methylphenidate, amphetamines, and guanfacine in children and adolescents, with efficacy plateaus.
- In adults, amphetamines showed a plateau, while methylphenidate efficacy continued to increase.
- Dose-dependent increases in discontinuation due to adverse events were noted for amphetamines and methylphenidate in adults.
Conclusions:
- Findings challenge therapeutic inertia and uncritical dose escalation beyond licensed limits.
- Results can inform clinical guidelines for ADHD medication dosage.
- The study supports shared decision-making in ADHD treatment regarding medication dosage.
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